OP0302 IS INCREASED RISK OF UROLITHIASIS IN AXIAL SPONDYLOARTHRITIS DRIVEN BY GUT INFLAMMATION? RESULTS FROM THE SPARTAKUS COHORT
Authors: J. K. Wallman, E. Mogard, J. Sagard, L. E. Kristensen, E. Lindqvist, T. Olofsson
Journal: Annals of the Rheumatic Diseases (2022)

Background A nationwide, Swedish study found a doubled urolithiasis risk in ankylosing spondylitis (AS) compared to population controls.[1] Inflammatory bowel disease (IBD) is a known risk factor for urolithiasis, e.g. via enteric hyperoxaluria causing calcium oxalate stones.[2] With microscopic gut inflammation in around 50% of axial spondyloarthritis (axSpA) patients,[3] and overt IBD in 5-10%, gut inflammation may also drive the increased urolithiasis risk in axSpA. Objectives To study whether axSpA patients with a history of urolithiasis have an increased prevalence of comorbid IBD or display elevated biomarkers of gut inflammation/pathology. Methods AxSpA patients in the population-based SPARTAKUS cohort study in southern Sweden (non-radiographic axSpA [nr-axSpA] n=86, ASAS criteria; AS n=168, modified New York criteria) self-reported their history of prior urolithiasis (no/yes). Faecal (F) calprotectin and ASCA (anti- Saccharomyces cerevisiae antibodies) in serum were measured by commercially available ELISAs (Calpro AS; ORGENTEC Diagnostika). For a subgroup of patients (n=164), presence of gut dysbiosis was also assessed by the GA-Map Dysbiosis Test (Genetic Analysis). Demographics, disease/treatment characteristics, comorbid IBD and the gastrointestinal biomarkers (F-calprotectin/ASCA/dysbiosis) were compared between patients with versus without prior urolithiasis. Finally, the same biomarkers were also compared between patients with versus without urolithiasis history, after exclusion of subjects with known IBD. Results Urolithiasis history was reported by 13% (n=33) of the axSpA patients, and comorbid IBD was significantly more common in this group (27% versus 6.8%, p&lt;0.001; Table 1). F-calprotectin levels were also significantly higher among patients with prior urolithiasis, as was presence of gut dysbiosis (Table 1). ASCA seropositivity did not differ between the groups. Moreover, prior urolithiasis was associated with longer disease duration and AS-phenotype. After exclusion of cases with comorbid IBD, urolithiasis history was reported by 10% (24 of 230 patients). F-calprotectin elevation ≥100 mg/kg remained significantly associated with urolithiasis history also in this population, while only being numerically increased when assessed as a continuous variable (p=0.053; Figure 1). Gut dysbiosis also remained associated with prior urolithiasis in the non-IBD population (56% [9 of 16 patients with prior urolithiasis] versus 30% [40 of 132 patients without], p=0.037), whereas ASCA status did not differ between the groups (data not shown). Table 1. Urolithiasis history No , n=221 Yes , n=33 Male sex 115 (52%) 23 (70%) Age, years 50 (13) 59 (12)* Disease duration, years 25 (14) 31 (14)* AS (versus nr-axSpA ) 141 (64%) 27 (82%)* Inflammatory bowel disease 15 (6.8%) 9 (27%)* ASAS 3-month NSAID score 31 (40) 37 (48) Ongoing bDMARD therapy 87 (39%) 16 (49%) bDMARD therapy ever 113 (51%) 20 (61%) ASDAS-CRP 1.8 (1.0) 1.9 (0.8) BASFI 2.0 (2.1) 2.7 (2.6) BASMI 2.9 (1.5) 4.3 (2.1)* F-Calprotectin, mg/kg *# Mean (SD) 58 (97) 115 (176) Median (IQR) 29 (49) 39 (152) F-Calprotectin ≥100 mg/kg 28 (14%) 10 (32%)* ASCA IgA ≥10 U/ml 12 (5.7%) 4 (13%) ASCA IgG ≥10 U/ml 45 (21%) 10 (33%) Gut dysbiosis † 45 (32%) 17 (71%)* Mean (SD) or n (%) if not otherwise stated. † GA-Map Dysbiosis Test, dysbiosis index ≥3. * p&lt;0.05 by Chi 2 -test or Student t-test, as appropriate. # Log 10 -transformed values compared. Missing ≤13%, except for gut dysbiosis available in 140/24 patients without/with urolithiasis history. Conclusion The current results lend support to the hypothesis that the increased urolithiasis risk in axSpA may be driven by gut inflammation/pathology. Prospective studies are, however, needed to assess the causality. References [1]Jakobsen AK, et al. PLoS One. 2014;9:e113602. [2]Corica D, et al. J Crohns Colitis. 2016;10:226-35. [3]Van Praet L, et al. Ann Rheum Dis. 2013;72:414-7. Disclosure of Interests Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Elisabeth Mogard Consultant of: Novartis, Jonas Sagard: None declared, Lars Erik Kristensen Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen Pharmaceuticals, Merck Sharp &amp; Dohme, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen Pharmaceuticals, Merck Sharp &amp; Dohme, Novartis, Pfizer, UCB Pharma, Elisabet Lindqvist: None declared, Tor Olofsson Consultant of: Eli Lilly, Merck Sharp &amp; Dohme